The invention relates to the preparation of and methods of using versatile fluorinated phosphonate synthons for constructing fluorine-containing organic compounds.
The use of fluorine in biologically active molecules is well known. One area of interest is the use of partially fluorinated phosphonates as phosphate mimics. The isosteric substitution of a hydrolytically labile ester oxygen of phosphate biomolecules by monofluoro- or difluoromethylene groups allows the latter to mimic the biological activity of the parent phosphates.
Recent reports of the antiviral and anticancer activities of partially fluorinated unsaturated phosphonucleosides have increased the demand for new methods for their synthesis (Harnden, M. R., et al. J. Med. Chem. 36, 1343-55, 1993; Megati, S., et al. J. Org. Chem. 57, 2320-27, 1992).
Syntheses of .alpha.,.alpha.-difluorophosphonates have been carried out in the past, mainly by utilizing the diethyl ester of difluoromethylene phosphonate. Other syntheses have made use of phosphonyl radical addition reactions and electrophilic fluorination.